title: Remodeling the integration of lipid metabolism between liver and adipose tissue by dietary methionine restriction in rats.
abstract: Dietary methionine restriction (MR) produces an integrated series of biochemical and physiological responses that improve biomarkers of metabolic health, limit fat accretion, and enhance insulin sensitivity. Using transcriptional profiling to guide tissue-specific evaluations of molecular responses to MR, we report that liver and adipose tissue are the primary targets of a transcriptional program that remodeled lipid metabolism in each tissue. The MR diet produced a coordinated downregulation of lipogenic genes in the liver, resulting in a corresponding reduction in the capacity of the liver to synthesize and export lipid. In contrast, the transcriptional response in white adipose tissue (WAT) involved a depot-specific induction of lipogenic and oxidative genes and a commensurate increase in capacity to synthesize and oxidize fatty acids. These responses were accompanied by a significant change in adipocyte morphology, with the MR diet reducing cell size and increasing mitochondrial density across all depots. The coordinated transcriptional remodeling of lipid metabolism between liver and WAT by dietary MR produced an overall reduction in circulating and tissue lipids and provides a potential mechanism for the increase in metabolic flexibility and enhanced insulin sensitivity produced by the diet.
authors.affiliation: Laboratories of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, Louisiana.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Hasek
authors.forename: Anik
authors.initials: A
authors.lastname: Boudreau
authors.forename: Jeho
authors.initials: J
authors.lastname: Shin
authors.forename: Daorong
authors.initials: D
authors.lastname: Feng
authors.forename: Matthew
authors.initials: M
authors.lastname: Hulver
authors.forename: Nancy T
authors.initials: NT
authors.lastname: Van
authors.forename: Amanda
authors.initials: A
authors.lastname: Laque
authors.forename: Laura K
authors.initials: LK
authors.lastname: Stewart
authors.forename: Kirsten P
authors.initials: KP
authors.lastname: Stone
authors.forename: Desiree
authors.initials: D
authors.lastname: Wanders
authors.forename: Sujoy
authors.initials: S
authors.lastname: Ghosh
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Pessin
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Gettys
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D004032:Diet; D015536:Down-Regulation; D004435:Eating; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D015870:Gene Expression; D007333:Insulin Resistance; D007930:Leucine / Q000172:deficiency*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000172:deficiency*; D008928:Mitochondria / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D008715:Methionine; D007930:Leucine